Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model)
<i>Background and Objectives</i>: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising t...
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MDPI AG
2023-05-01
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| Series: | Medicina |
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| Online Access: | https://www.mdpi.com/1648-9144/59/5/1000 |
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| author | Matthias Troeltzsch Stephan Zeiter Daniel Arens Dirk Nehrbass Florian A. Probst Paris Liokatis Michael Ehrenfeld Sven Otto |
| author_facet | Matthias Troeltzsch Stephan Zeiter Daniel Arens Dirk Nehrbass Florian A. Probst Paris Liokatis Michael Ehrenfeld Sven Otto |
| author_sort | Matthias Troeltzsch |
| collection | DOAJ |
| description | <i>Background and Objectives</i>: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising theory suspects infectious stimuli and local acidification with adverse effects on osteoclastic activity as crucial steps of MRONJ etiology. Clinical evidence showing a direct association between MRONJ and oral infections, such as periodontitis, without preceding surgical interventions is limited. Large animal models investigating the relationship between periodontitis and MRONJ have not been implemented. It is unclear whether the presence of infectious processes without surgical manipulation can trigger MRONJ. The following research question was formulated: is there a link between chronic oral infectious processes (periodontitis) and the occurrence of MRONJ in the absence of oral surgical procedures? <i>Materials and Methods:</i> A minipig large animal model for bisphosphonate-related ONJ (BRONJ) using 16 Göttingen minipigs divided into 2 groups (intervention/control) was designed and implemented. The intervention group included animals receiving i.v. bisphosphonates (zoledronate, n = 8, 0.05 mg/kg/week: ZOL group). The control group received no antiresorptive drug (n = 8: NON-ZOL group). Periodontitis lesions were induced by established procedures after 3 months of pretreatment (for the maxilla: the creation of an artificial gingival crevice and placement of a periodontal silk suture; for the mandible: the placement of a periodontal silk suture only). The outcomes were evaluated clinically and radiologically for 3 months postoperatively. After euthanasia a detailed histological evaluation was performed. <i>Results:</i> Periodontitis lesions could be induced successfully in all animals (both ZOL and NON-ZOL animals). MRONJ lesions of various stages developed around all periodontitis induction sites in the ZOL animals. The presence of MRONJ and periodontitis was proven clinically, radiologically and histologically. <i>Conclusions:</i> The results of this study provide further evidence that the infectious processes without prior dentoalveolar surgical interventions can trigger MRONJ. Therefore, iatrogenic disruption of the oral mucosa cannot be the decisive step in the pathogenesis of MRONJ. |
| first_indexed | 2024-03-11T03:29:56Z |
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| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-11T03:29:56Z |
| publishDate | 2023-05-01 |
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| spelling | doaj.art-03f0063b0c284661b5900732af2a234a2023-11-18T02:23:31ZengMDPI AGMedicina1010-660X1648-91442023-05-01595100010.3390/medicina59051000Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model)Matthias Troeltzsch0Stephan Zeiter1Daniel Arens2Dirk Nehrbass3Florian A. Probst4Paris Liokatis5Michael Ehrenfeld6Sven Otto7Department of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, LMU Munich, Lindwurmstraße 2a, 80337 Munich, GermanyAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandAO Research Institute Davos, Clavadelerstrasse 8, 7270 Davos, SwitzerlandDepartment of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, LMU Munich, Lindwurmstraße 2a, 80337 Munich, GermanyDepartment of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, LMU Munich, Lindwurmstraße 2a, 80337 Munich, GermanyDepartment of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, LMU Munich, Lindwurmstraße 2a, 80337 Munich, GermanyDepartment of Oral and Maxillofacial Surgery and Facial Plastic Surgery, University Hospital, LMU Munich, Lindwurmstraße 2a, 80337 Munich, Germany<i>Background and Objectives</i>: Antiresorptive drugs are widely used in osteology and oncology. An important adverse effect of these drugs is medication-induced osteonecrosis of the jaw (MRONJ). There is scientific uncertainty about the underlying pathomechanism of MRONJ. A promising theory suspects infectious stimuli and local acidification with adverse effects on osteoclastic activity as crucial steps of MRONJ etiology. Clinical evidence showing a direct association between MRONJ and oral infections, such as periodontitis, without preceding surgical interventions is limited. Large animal models investigating the relationship between periodontitis and MRONJ have not been implemented. It is unclear whether the presence of infectious processes without surgical manipulation can trigger MRONJ. The following research question was formulated: is there a link between chronic oral infectious processes (periodontitis) and the occurrence of MRONJ in the absence of oral surgical procedures? <i>Materials and Methods:</i> A minipig large animal model for bisphosphonate-related ONJ (BRONJ) using 16 Göttingen minipigs divided into 2 groups (intervention/control) was designed and implemented. The intervention group included animals receiving i.v. bisphosphonates (zoledronate, n = 8, 0.05 mg/kg/week: ZOL group). The control group received no antiresorptive drug (n = 8: NON-ZOL group). Periodontitis lesions were induced by established procedures after 3 months of pretreatment (for the maxilla: the creation of an artificial gingival crevice and placement of a periodontal silk suture; for the mandible: the placement of a periodontal silk suture only). The outcomes were evaluated clinically and radiologically for 3 months postoperatively. After euthanasia a detailed histological evaluation was performed. <i>Results:</i> Periodontitis lesions could be induced successfully in all animals (both ZOL and NON-ZOL animals). MRONJ lesions of various stages developed around all periodontitis induction sites in the ZOL animals. The presence of MRONJ and periodontitis was proven clinically, radiologically and histologically. <i>Conclusions:</i> The results of this study provide further evidence that the infectious processes without prior dentoalveolar surgical interventions can trigger MRONJ. Therefore, iatrogenic disruption of the oral mucosa cannot be the decisive step in the pathogenesis of MRONJ.https://www.mdpi.com/1648-9144/59/5/1000periodontitisMRONJminipig animal modelchronic inflammationosteonecrosisperiodontitis induction |
| spellingShingle | Matthias Troeltzsch Stephan Zeiter Daniel Arens Dirk Nehrbass Florian A. Probst Paris Liokatis Michael Ehrenfeld Sven Otto Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model) Medicina periodontitis MRONJ minipig animal model chronic inflammation osteonecrosis periodontitis induction |
| title | Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model) |
| title_full | Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model) |
| title_fullStr | Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model) |
| title_full_unstemmed | Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model) |
| title_short | Chronic Periodontal Infection and Not Iatrogenic Interference Is the Trigger of Medication-Related Osteonecrosis of the Jaw: Insights from a Large Animal Study (PerioBRONJ Pig Model) |
| title_sort | chronic periodontal infection and not iatrogenic interference is the trigger of medication related osteonecrosis of the jaw insights from a large animal study periobronj pig model |
| topic | periodontitis MRONJ minipig animal model chronic inflammation osteonecrosis periodontitis induction |
| url | https://www.mdpi.com/1648-9144/59/5/1000 |
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